tbuckley/cabot-search huggingface dataset:
Comparison of DNA sequencing, immunohistochemistry, and in-situ hybridization techniques to determine HER2 status in metastatic breast cancer patients.
Authors: Lincy S. Lal, Dana Milne, Mark S. Walker, Marina Kovach
Journal: Journal of Clinical Oncology (2022)

e13045 Background: Limited studies exist comparing methods for HER2 status determination using real-world data (RWD). Results of metastatic breast cancer (MBC) patients with Next Generation Sequencing (NGS) within the ConcertAI Genome360 dataset with DNA sequencing were compared to the standard immunohistochemistry (IHC) or in-situ hybridization (ISH) or both IHC and ISH for HER2 status. Methods: Patients diagnosed with MBC, with HER2 status determined with NGS DNA sequencing, IHC, or any of the ISH tests, by various laboratories within 2 months of each other, from August 19, 2011 to March 9, 2021, were analyzed. Patients were classified as positive, negative, or equivocal based on each of the testing methods. Comparisons were made between DNA sequencing and IHC results, DNA and ISH results, and DNA and IHC and subsequent ISH results. Results: The study sample included 252 patients (99% female, mean age [SD] of 62 [11.93]) with 382 test combinations as follows: 220 (58%) with DNA sequencing and IHC results, 127 (33%) with DNA sequencing and ISH results, and 35 (9%) with DNA sequencing and IHC and ISH results. Of the 220 combinations with DNA sequencing and IHC results, 15 were uniformly considered HER2+, 160 HER2-, and 1 equivocal, while 44 differed in the results, resulting in 80% match rate. Of the 127 combinations with DNA sequencing and ISH results, 14 were HER2+ and 96 HER2-, while 17 differed, resulting in 87% match rate. Of the 35 combinations with DNA sequencing and IHC and ISH, 3 were HER2+ and 26 were HER2-, while 6 differed, resulting in 83% match rate. Match rate was significantly higher for patients with negative results, than positive results. Specimen type, site, and type of expression had no impact on match rates. Conclusions: RWD indicate relatively high level of match rate among DNA sequencing, IHC, and ISH results in MBC patients. However, 13-20% of the combinations did not match. For these patients, mechanisms to reach consensus need to be explored to determine optimal treatments.
Evolution of Plasmid Mobility: Origin and Fate of Conjugative and Nonconjugative Plasmids
Authors: Charles Coluzzi, Maria Pilar Garcillán-Barcia, Fernando de la Cruz, Eduardo P.C. Rocha
Journal: Molecular Biology and Evolution (2022)

Abstract Conjugation drives the horizontal transfer of adaptive traits across prokaryotes. One-fourth of the plasmids encode the functions necessary to conjugate autonomously, the others being eventually mobilizable by conjugation. To understand the evolution of plasmid mobility, we studied plasmid size, gene repertoires, and conjugation-related genes. Plasmid gene repertoires were found to vary rapidly in relation to the evolutionary rate of relaxases, for example, most pairs of plasmids with 95% identical relaxases have fewer than 50% of homologs. Among 249 recent transitions of mobility type, we observed a clear excess of plasmids losing the capacity to conjugate. These transitions are associated with even greater changes in gene repertoires, possibly mediated by transposable elements, including pseudogenization of the conjugation locus, exchange of replicases reducing the problem of incompatibility, and extensive loss of other genes. At the microevolutionary scale of plasmid taxonomy, transitions of mobility type sometimes result in the creation of novel taxonomic units. Interestingly, most transitions from conjugative to mobilizable plasmids seem to be lost in the long term. This suggests a source-sink dynamic, where conjugative plasmids generate nonconjugative plasmids that tend to be poorly adapted and are frequently lost. Still, in some cases, these relaxases seem to have evolved to become efficient at plasmid mobilization in trans, possibly by hijacking multiple conjugative systems. This resulted in specialized relaxases of mobilizable plasmids. In conclusion, the evolution of plasmid mobility is frequent, shapes the patterns of gene flow in bacteria, the dynamics of gene repertoires, and the ecology of plasmids.
Treatment patterns and their impact on the outcome of patients with HR+/HER2+ metastatic breast cancer in a large real-world cohort.
Authors: Marcela Carausu, Matthieu Carton, Veronique C Dieras, Thierry Petit, Severine Guiu Lahaye, Corinne Veyret, Anthony Goncalves, Paule Augereau, Jean-Marc Ferrero, Christelle Levy, Mony Ung, Isabelle Desmoulins, Marc Debled, Thomas Bachelot, Jean-Christophe Eymard, Barbara Pistilli, Jean-Sebastien Frenel, Michaël Chevrot, Audrey Mailliez, Luc Cabel
Journal: Journal of Clinical Oncology (2022)

1043 Background: The place of endocrine therapy (ET) in the treatment of hormone receptor-positive (HR+), HER2+ metastatic breast cancer (MBC) is still not clearly defined. Data suggest that blocking both HR and HER2 signaling pathways could be an efficacious strategy to overcome secondary resistance. Methods: We aimed to retrospectively evaluate the impact of first line (L1) therapy for HR+/HER2+ MBC patients (pts) included between 2008- 2017 in the French real-world ESME MBC database (NCT03275311). Our primary endpoints were median overall survival (mOS) and median first progression-free survival (mPFS1). We used descriptive statistics and the Kaplan-Meier method to report patient characteristics and outcomes. Cox proportional hazards models and a propensity score were constructed to report and adjust for prognostic factors. Results: From the 23,501 female pts in the ESME MBC cohort, 1,790 pts had HR+/HER2+ MBC treated with Trastuzumab (T, n=1,089) or Trastuzumab-Pertuzumab (TP, n=701) during L1. Among them, 1,584 pts received antiHER2 therapy+CT+/-ET and 206 pts, antiHER2+ET only. Pts with antiHER2+CT+/-ET had more often ECOG performance status 0 (29.5% vs 15.8%, p&lt;0.001), grade III tumors (36.6% vs 25.6%, p=0.007), time to MBC &lt; 6 mo (51.6% vs 29.1%, p&lt;0.001), TP as antiHER2 therapy (43.2% vs 9.4%, p&lt;0.001), ≥3 metastatic sites (23.2% vs 14.8%, p=0.007), visceral metastasis (56.5% vs 42.4%, p&lt;0.001), and less often bone-only disease (18.4% vs 35%, p&lt;0.001) than pts with antiHER2+ET. In multivariable analysis, antiHER2+CT+/-ET was not superior to antiHER2+ET (Table), while TP was superior to Trastuzumab, and this result was confirmed by matching pts using a propensity score ( p=0.76 for mOS and p=0.85 for mPFS1). Using the time-dependent ET variable among pts with antiHER2+CT, pts with maintenance ET had significantly better PFS1 and OS than those without (adjusted HR for PFS1=0.70 [95%CI 0.60-0.82], adjusted HR for OS=0.47 [95%CI 0.39-0.57], p&lt;0.001). Conclusions: These data suggest that endocrine therapy could be an interesting less toxic alternative to chemotherapy in combination with antiHER2 therapy as first line treatment for HR+/HER2+ MBC pts.[Table: see text]
The correlation between tumor mutation burden and <i>TP53</i> or <i>CHEK2 </i>germline mutations in malignant tumors.
Authors: Xiaohui Gao, Yali Zhang, Mengmeng Li, Yaqing Wu, Ningning Luo, Xiaofeng Zhu, Yingxue Qi, Tingting Sun, Chuang Qi
Journal: Journal of Clinical Oncology (2022)

e22527 Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome, mainly caused by the lack of tumor suppressor gene TP53. The LFS related tumors include breast cancer, brain tumors, malignant sarcoma, bone cancer and central nervous system tumors. In addition to TP53 germline mutations, studies have shown that CHEK2 is also a susceptibility gene for LFS, and CHEK2 germline mutations is related to a series of cancer types. However, the correlation between tumor mutation burden (TMB), age, gender, PD-L1 expression and TP53 or CHEK2 germline mutations in malignant tumors remains unknown. Methods: In this study, we retrospectively analyzed the mutation characteristics of TP53 or CHEK2 germline mutations in patients with solid tumors without selecting age or family history. We identified 631 patients harboring TP53 or CHEK2 mutations from 9337 patients with malignant solid tumors. According to the ACMG (American College of Medical Genetics and Genomics) guidelines in pathogenicity, the 631 patients in the retrospective cohort were divided into three groups, including P/LP group (with pathogenic or likely-pathogenic mutations), VUS group (with uncertain significance mutations) and B/LB group (with benign or likely-benign mutations). We also analyzed the differences in TMB, age, gender and PD-L1 expression among the three groups. Statistical significance was defined as P-value less than 0.05. Results: The 631 (631/9337) patients carried TP53 or CHEK2 germline mutations were identified, in which 33 patients with pathogenic mutations and 15 patients with likely-pathogenic mutations. These pathogenic or likely-pathogenic mutations mainly occurred in lung cancer, brain tumors, colorectal cancer and liver cancer, accounting for about 35.4%, 20.8%, 16.7% and 12.5%, respectively. Among the three groups, TMB was significantly different between P/LP group and B/LB group (P = 0.037), and the B/LB group was higher. In addition, we found that the three groups had no significant differences in age, gender and PD-L1 expression. Conclusions: Our data showed that 0.823% (48/8535) malignant solid tumor patients carried TP53 (28/48) or CHEK2 (20/48) germline pathogenic or likely_ pathogenic mutations. In addition, the TMB value in B/LB group was significantly higher than that in P/LP group. The other characteristics of LFS will be studied in the future.
A comparison of dosimetry and clinical outcomes in patients receiving photon external beam therapy to the pelvis: A two-year experience with 6MV and 10MV photon energies in cervical cancer patients at Parirenyatwa Radiotherapy Centre in Harare, Zimbabwe.
Authors: Chimwemwe Moses Banda, Ntokozo Ndlovu, Albert Nyamhunga
Journal: Journal of Clinical Oncology (2022)

e18768 Background: Radiotherapy efficacy depends on the ability of the treatment machine to deliver optimal radiation dose to target volume while sparing normal tissue using different techniques. The photon energy determines penetrative power. Higher photon energies are generally preferred over low photon energies when treating deep tumours using 3-dimensional conformal radiotherapy (3DCRT). In most low income settings, availability of higher energies (≥10MV) is limited. Elsewhere protocols do not recommend use of lower energies for deep pelvic tumours. There is paucity of data comparing 10MV and 6MV photon energy plans and outcomes for treatment of pelvic tumours with 3DCRT. This study aimed to compare dosimetric and clinical tumour outcomes between the two photon energies which are available in our setting when treating locally advanced cervical cancer (LACC). Methods: We retrospectively analysed medical records for LACC patients who received definitive concurrent chemoradiotherapy (CCRT) at Parirenyatwa Group of Hospitals Radiotherapy Centre for the period between 1 st January 2017 and 31 st December 2018. Patient’s treatment plans were stratified into two arms according to the photon energies used (10MV and 6MV) and their respective dosimetric and clinical tumour outcomes at three months post-treatment were compared. Results: A total 875 cervical cancer patients were seen during the study period, of these 82 met the inclusion criteria and were evaluated. Out of these, 20(24.4%) and 62(75.6%) patients were planned and/or treated with 10MV and 6MV photon energy respectively. The differences in minimum doses to the planned target volume and dose homogeneity index between the two photon energies were statistically significant (p-values 0.027 and 0.028 respectively), whereas the other dosimetric parameters (maximum &amp; average doses to the planned target volume, conformity index and maximum doses to rectum, bladder, femoral heads and bowel) were not statistically significant (p-values of 0.245, 0.309, 0.130, 0.19, 0.35 and 0.42, and 0.16 respectively). Complete clinical tumour response at 3 months post treatment was 95% in the 10 MV arm compared to 91% in the 6 MV arm. Conclusions: This study showed that the dosimetric and clinical tumour outcomes in LACC patients receiving 3DCRT definitive CCRT using 10MV or 6MV photon energy in our setting are comparable. Follow-up prospective studies to further characterise the application of these photon energies in resource constrained settings is recommended.
Assessment of COVID vaccine knowledge and hesitancy in an ethnic minority oncology patient population.
Authors: Matthew Lee, Emily Miao, Shankar Viswanathan, Bruce D. Rapkin, Balazs Halmos, Sanjay Goel
Journal: Journal of Clinical Oncology (2022)

e18570 Background: Complicating the pandemic are the healthcare disparities experienced by ethnic minorities, including Black and Hispanic Americans. This is further exacerbated in those ethnic subgroups, especially if they have comorbidities, including cancer. With the introduction of COVID-19 vaccines, the shift is now focused on promoting vaccination. However, vaccine hesitancy and motives of why ethnic minority cancer patients receive or do not receive vaccines have not been explored and are the focus of this study. Methods: A cross-sectional survey was administered among cancer patients to understand the knowledge and attitude towards COVID-19 vaccines at a single institution in a predominantly ethnic minority population between February 1-June 30, 2021. The participant's inclusion criteria were &gt;18 years old and diagnosed with solid or hematologic malignancy. Descriptive statistics were used to summarize the patient characteristics, COVID-19 vaccine knowledge, and uptake motives. A composite score of COVID-19 and vaccine knowledge was derived and its role on vaccination status was assessed using a multivariable logistic regression model. Results: Of 52 patients surveyed, COVID-19 vaccination prevalence during the survey was 40.4% (95% CI: 27, 54.9). Participants' average (sd) age was 63.5 (13.6) years; 42% were male, 36% were Black, and 30% Hispanic; 65% were receiving active treatment for their cancer. Seventy-nine percent believed COVID-19 infection to be dangerous or harmful to them, 61% were concerned about the side effects of the COVID-19 vaccine, yet 65% considered vaccines safe. Those refusing the vaccine (n=7) cited side effects (71%) or believed that the vaccine was not needed (57%). Of those who were unvaccinated (n=31), 48.4% (n=15) got vaccinated post-survey. The odds of vaccination was 3.79 (1.63, 8.82) times higher with a 1 unit increase in COVID-19 knowledge score but was not significant in the multivariable model. The final model suggested that the odds of vaccination increased 2.9 times more for a 1 unit increase in vaccine knowledge score; Blacks were two times more likely to get vaccinated and those with more than high school education had a five-fold increase in vaccination. The model results are presented in Table. Conclusions: This exploratory study has demonstrated that there are multiple reasons why an ethnic minority cancer patient would be vaccinated and possible reasons why they would not. This information will become important in improving vaccine campaigns targeting these populations and ensuring their safety and protection against COVID-19.[Table: see text]
PEACE V – Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): Acute toxicity of a randomized phase II trial
Authors: P. Ost, S. Siva, R. Heikkilä, P. Dirix, N. Liefhooghe, F-X. Otte, A. Gomez-Iturriaga, W. Everaerts, M. Shelan, A. Conde-Moreno, F. Lopez Campos, A. Papachristofilou, M. Guckenberger, M. Scorsetti, A. Zapatero, A-E. Villafranca Iturre, C. Eito, F. Couñago, P. Muto, L. Van De Voorde, V. Fonteyne, D. Reynders, T. Zilli
Journal: European Urology (2022)
QOL-25. Neurocognitive assessment of pediatric medulloblastoma treated by MBMET_MEYER trial. Censullo M.L1, Bertoluzzo G2, Fonte C1, Pavone R1, Guidi M1, Enrico G1, Gori C.G1, Martin R2, Teodori C2, Sardi I1 1Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s University Hospital, Florence, Italy2Psychology Unit, Meyer Children’s University Hospital, Florence, Italy
Authors: Maria Luigia Censullo, Giulia Bertoluzzo, Carla Fonte, Rossana Pavone, Milena Guidi, Enrico Giorgia, Carlotta Gemma Gori, Rosanna Martin, Caterina Teodori, Iacopo Sardi
Journal: Neuro-Oncology (2022)

Abstract The MBMET_MEYER is an interventistic monocentric trial of Meyer Children’s Hospital. The goal of this protocol is to reduce toxicity by use of protontherapy and reducing chemo-induced neurotoxicity by limited use of high dose chemotherapy. To date, a neurocognitive assessment is the standard in medulloblastomas but it is very difficult an assessment at baseline for clinical problems such as age, intracranial hypertension and immediate intervention. 10 neurocognitive assessments were reviewed in patients with medulloblastoma treated by MBMET_MEYER protocol: 3 anaplastic medulloblastoma M0 and 7 classic (2 M0, 1 M1, 1 M2, 3 M3). The median age was 10 years (range 5-18). All the patients were treated with surgery (gross total removal), 2 received chemotherapy and conventional radiotherapy, 8 chemotherapy and protontherapy and only 1 received autologos-hemotopoietic stem cell transplant for progression disease after induction chemotherapy. As for protocol, the neurocognitive assessment was defined by Weschler Intelligence Scales, fonemic and semantic fluency, immediate and deferred memory, tests for working memory, attention and visuo-spatial tests at baseline, after treatment and at the end of follow-up. For 3 patients it was not possible a baseline assessment for bad clinic conditions, 8 are still in treatment. From interviews and assessments emerged that 80% of patients had neurocognitive deficits: at baseline 5 had speed elaboration difficulties, 1 of these also presented verbal deficit, 1 showed problems in recalling verbal material and 1 in working memory; after two years from chemotherapy and radiotherapy 2 presented speed processig and working memory deficit. In conclusion, an assessment at baseline is very difficult for post-surgical problems but necessary to perform as soon. In this way, it is possible to evaluate the impact of the treatment on neurocognitive impairment. Further investigations are necessary to well understand the appropriate schedule of neurocognitive assessment of pediatric medulloblastoma.
Medication for Early Pregnancy Termination
Authors: Rebecca H. Cohen, Stephanie B. Teal
Journal: JAMA (2022)

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Novel framework for treatment response evaluation using PSMA-PET/CT in patients with metastatic castration-resistant prostate cancer (RECIP 1.0): An international multicenter study
Authors: A. Gafita, I. Rauscher, M.E. Weber, B. Hadaschik, H. Wang, W.R. Armstrong, R. Tauber, T.R. Grogan, J. Czernin, M.B. Rettig, K. Herrmann, J. Calais, W. Weber, M.R. Benz, W.P.W Fendler, M. Eiber
Journal: European Urology (2022)
Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis.
Authors: Joyce O'Shaughnessy, Achim Woeckel, Barbara Pistilli, Roberto Hegg, Linda T. Vahdat, Dragica Vuina, Parisa(Fatemeh) Asad ZVK, Timothy W Smith, Julia Kim, Ian Krop
Journal: Journal of Clinical Oncology (2022)

1055 Background: ALP (α-selective PI3K inhibitor and degrader) + FUL was FDA approved and reflected in the NCCN guidelines in 2019 for pts with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) ABC with PIK3CA mutations following progression on or after endocrine-based therapy (ET). The Phase III SOLAR-1 trial excluded prior FUL, and data on ALP + FUL after FUL are limited. As cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + ET (including FUL) is the standard in the first line (1L) or second line (2L) for pts with HR+/HER2− ABC, more data on ALP + FUL post-FUL are needed. Here we report patterns and clinical outcomes on RW use of ALP + FUL in pts with HR+/HER2– ABC with prior FUL exposure. Methods: This retrospective study used de-identified electronic health record data from the ConcertAI Patient360 Breast Cancer data product sourced from US oncology centers. Adults with HR+/HER2− ABC treated with ALP + FUL (index tx) who received prior FUL (monotherapy or in combination) in the metastatic setting were included; pts with a PIK3CA negative test on or prior to the index were excluded. Pts were followed until date of death or last activity. RW progression-free survival (rwPFS), defined as first documented progression/death from ALP + FUL start date, was assessed. Results: This analysis included 157 pts (median age, 63 y [57-71 y]) who received ALP + FUL from 2019 to 2021, with 11.5% pts in 1L, 17.8% in 2L, 26.8% in third line (3L), and 43.9% in fourth line and beyond (4L+). Prior FUL tx included CDK4/6i + FUL (74.5%), FUL alone (33.8%), and non-CDK4/6i + FUL (21.0%). In pts who received ALP + FUL in 1L (n = 18), prior FUL exposure was in the same line without documented progression. In the metastatic setting, 28.0% of pts received &gt; 1 FUL-containing regimen and/or 72.0% received prior chemotherapy (CT). At the median duration of follow-up (8.7 mo [4.1-12.5 mo]), the median rwPFS was 5.7 mo (4.0-7.3 mo) in the overall population. The median rwPFS was also analyzed by line of therapy (Table). In pts with CDK4/6i + FUL as immediate prior therapy (n = 39), the median rwPFS was 6.2 mo (3.0-9.1 mo); 79.5% of these pts received ALP in ≤ 3L. At the time of analysis, 107 pts (68.2%) had discontinued ALP + FUL; the median time to discontinuation was 4.7 mo (3.7-6.1 mo). Following discontinuation of ALP + FUL, CT was the most common subsequent therapy (33.8%). Conclusions: This analysis on RW data from early years of ALP access in the US shows clinical benefit of ALP + FUL in pts with HR+/HER2− ABC with PIK3CA mutation even when exposed to prior FUL, confirming the oncogenic dependence of the tumor on the PIK3CA mutation. [Table: see text]